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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
1996-3-20
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pubmed:abstractText |
1. Besipirdine (HP 749) is a compound undergoing clinical trials for efficacy in treating Alzheimer's disease. Among other pharmacological effects, besipirdine inhibits voltage-dependent sodium and potassium channels. This paper presents a pharmacological study of the interaction of besipirdine with voltage-dependent sodium channels. 2. Besipirdine inhibited [3H]-batrachotoxin binding (IC50 = 5.5 +/- 0.2 microM) in a rat brain vesicular preparation and concentration-dependently inhibited veratridine (25 microM)-stimulated increases in intracellular free sodium ([Na+]i) and calcium ([Ca2+]i) in primary cultured cortical neurones of rat. 3. Besipirdine (30-100 microM) concentration-dependently inhibited (up to 100%) veratridine-stimulated release of [3H]-noradrenaline (NA) from rat cortical slices. 4. When examined in greater detail, besipirdine was found to inhibit [3H]-batrachotoxin binding in vesicular membranes competitively. However, when examined in rat brain synaptosomes, we found that the antagonism by besipirdine was not competitive; that is, the maximal stimulation of [Ca2+]i induced by veratridine decreased with increasing concentrations of besipirdine. 5. These results show that besipirdine is an inhibitor of voltage-sensitive sodium channels and appears to bind to a site close to the batrachotoxin/veratridine binding site.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/8581286-13008534,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8581286-1331817,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8581286-2426426,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8581286-2427018,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8581286-2453211,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8581286-2456998,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8581286-2810583,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8581286-2880938,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8581286-6114956,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8581286-6300644,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8581286-7891842,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8581286-8295214,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8581286-8301556,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8581286-8394919,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8581286-925017
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Batrachotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Neurotransmitter Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Norepinephrine,
http://linkedlifedata.com/resource/pubmed/chemical/Parasympatholytics,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Veratridine,
http://linkedlifedata.com/resource/pubmed/chemical/besipirdine
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0007-1188
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
116
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2468-72
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:8581286-Animals,
pubmed-meshheading:8581286-Batrachotoxins,
pubmed-meshheading:8581286-Calcium,
pubmed-meshheading:8581286-Cells, Cultured,
pubmed-meshheading:8581286-Electrophysiology,
pubmed-meshheading:8581286-Indoles,
pubmed-meshheading:8581286-Ion Channel Gating,
pubmed-meshheading:8581286-Kinetics,
pubmed-meshheading:8581286-Male,
pubmed-meshheading:8581286-Neurotransmitter Agents,
pubmed-meshheading:8581286-Norepinephrine,
pubmed-meshheading:8581286-Parasympatholytics,
pubmed-meshheading:8581286-Pyridines,
pubmed-meshheading:8581286-Rats,
pubmed-meshheading:8581286-Rats, Sprague-Dawley,
pubmed-meshheading:8581286-Rats, Wistar,
pubmed-meshheading:8581286-Sodium,
pubmed-meshheading:8581286-Sodium Channels,
pubmed-meshheading:8581286-Synaptosomes,
pubmed-meshheading:8581286-Veratridine
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pubmed:year |
1995
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pubmed:articleTitle |
Effects of besipirdine at the voltage-dependent sodium channel.
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pubmed:affiliation |
Department of Biological Research, Hoechst Roussel Pharmaceuticals, Inc., Somerville, NJ 08876, USA.
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pubmed:publicationType |
Journal Article,
In Vitro
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